Sex differences in pulmonary hypertension: are we cleaning up the mess?

When I was looking for a research project to pursue as a fellow in 2006, I became interested in sex differences in pulmonary arterial hypertension (PAH). When I proposed the idea of pursuing this topic further to a well-regarded expert in the field, his sobering answer was “That area is a mess”; and what a mess it was! We knew at that time that oestrogens exert protective effects in acute and chronic hypoxia-induced pulmonary hypertension (PH) [1–3], as well as in monocrotaline-induced PH (MCT–PH) [4]. However, we also knew that women are more prone to PAH [5], a finding at odds with the data derived from animal studies. Soon after that, we learned that women, despite being more prone to PAH development, exhibit better survival and better right ventricular function than their male counterparts [6, 7]. The superior survival in female patients ultimately was linked at least in part to improved right ventricular function [8, 9]. Epidemiological studies in healthy subjects implicated oestrogens and dehydroepiandrosterone as mediators of superior right ventricular function, whereas testosterone was associated with higher right ventricular mass, higher volumes and lower right ventricular ejection fraction (RVEF) [10]. Genomic and non-genomic factors determine disparate right ventricular and pulmonary vascular effects of sex steroids http://ow.ly/WdBNQ